Experts agree that leaving pregnant and lactating populations out of clinical trials can cause harm and create uncertainty for both mother and baby. During the national webinar and congressional briefing, “Pregnant and Lactating Populations in Research: How Leaving These Populations Out Leaves Them Behind,” part two of a three-part series hosted by the Coalition to Advance Maternal Therapeutics (CAMT), panelists Christina Chambers, PhD, MPH (moderator), University of California, San Diego; Anne Drapkin Lyerly, MD, MA, University of North Carolina Chapel Hill; and Kara Polen, MPH, U.S. Centers for Diesease Control and Prevention (CDC) discussed the consequences that society faces when these key populations are excluded from clinical trials.
Dr. Chambers began the event by providing an overview of the dilemma that pregnant and lactating women—or those wishing to become pregnant—may face: trying to determine if a medication they take is safe for their child. She shared that every day at the organization MotherToBaby, there are women reaching out to counselors saying, “I just found out I’m pregnant, and I’m worried my asthma medication/the antidepressant medication I take/the treatment I need for my psoriasis, etc. could harm my baby.” Similarly, there are women who reach out to the organization who wish to become pregnant but are worried about the risk that the medication they take to treat their condition could pose. When pregnant and lactating women are not included in clinical trials, women and their health care providers are left to make decisions without adequate information.
Building off this point, Dr. Lyerly reviewed the critical and “profoundly harmful” evidence gaps that have emerged because of the exclusion of pregnant and lactating populations in clinical trials. She reviewed gaps within three key areas:
- Dosing. Not understanding a medication’s effect on a pregnant body can lead to ineffective treatment. Pregnant women, who experience changes in physiology, could be under-treated and remain exposed to the harms of disease or over-treated and exposed to excess toxicity of drugs.
- Fetal Safety. Women cannot and do not presume the drugs they’re prescribed are safe, and their prescribed medications may be unsafe for the fetus.
- Maternal Outcomes. Dr. Lyerly noted, given gaps on maternal outcomes, medications that are deemed safe for the fetus may carry inappropriate risk for the pregnant person. Further, the reticence of women to use medications and vaccines out of fetal safety concerns and the resultant failure to treat may harm both the pregnant person and the fetus. The harms of under-treatment may outweigh the risks of medication use. As Dr. Lyerly summarized, “Disease itself can be an important teratogen.”
As Dr. Lyerly said in her presentation, “While excluding pregnant women from research prevents risk in research contexts, the risk doesn’t disappear. Instead, risks shift to the clinical setting, where they expand.”
The COVID-19 pandemic was an example of this. As decribed by Polen, for the initial COVID-19 vaccine clinical trials, pregnant people were excluded because of theoretical risks to the fetus. When COVID-19 vaccines were authorized for use in December 2020, there was very limited safety data available about use in pregnancy.
In April 2021, the first safety data on the COVID-19 vaccine emerged and found no safety concerns for pregnant people vaccinated in the third trimester or for their babies, no increased risk of miscarriage among pregnant people vaccinated before 20 weeks, and data suggested mRNA COVID-19 vaccines during pregnancy were effective. However, during that point, rumors, including that the COVID-19 vaccine led to infertility and caused damage to the placenta, had begun to circulate. Further, there was inconsistent guidance globally, which caused confusion among pregnant people and their families.
In fall of 2021, CDC strengthened guidance on COVID-19 vaccination during pregnancy and lactation, but at that point, the Delta variant had ramped up and resulted in devastating outcomes, including increases in maternal ICU admissions, deaths, and stillbirths among unvaccinated women who were pregnant (pregnant people with COVID had four times the risk of having a stillbirth compared to other time periods).
While CDC leveraged existing vaccine safety monitoring systems and rapidly launched new systems to monitor and follow up on the health of pregnant people who received vaccines and their babies, the absence of early clinical trial data on this population prevented a strong recommendation for the COVID-19 vaccination pregnancy for 8 months, led states to differentially include pregnancy as an eligible condition and providers to offer inconsistent guidance to patients, allowed a vacuum for the spread of misinformation, and likely contributed to hesitancy and lower acceptance of other vaccines.
Including pregnant and lactating populations in clinical trials early is necessary for preventing situations like this in the future. In addition, Dr. Lyerly shared three conceptual shifts that are needed when we talk about the inclusion of pregnant and lactating populations in research, each of which echo points from panelists during the first briefing of this series:
- Move from speaking about these groups as a “vulnerable population” to speaking about them as a “complex population;”
- Think about these populations’ inclusion in research as protecting them through research, not “protection from research;” and
- Move from “presumptive exclusion” to the “fair inclusion” of these populations in clinical trials.
To hear additional takeaways from this congressional briefing, view the recording online.
0 Comments